Antibacterial compositions comprising quaternary ammonium germicides and alkamine oxides having reduced irritation potential

ABSTRACT

Antibacterial compositions having antibacterial effectiveness and reduced eye irritation potential are disclosed. The antibacterial compositions contain a quaternary ammonium compound, an alkamine oxide, a nonionic compound, optional adjuvant materials known in the art, and water. The eye irritation is decreased by decreasing the amount, by weight, of alkamine oxide present in the composition and alternatively, or in combination therewith, increasing the ratio of nonionic material to alkamine oxide present in the composition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Phase filing under 35 U.S.C. 371 andclaims priority to PCT Application No. PCT/US2006/048991, entitled“ANTIBACTERIAL COMPOSITIONS COMPRISING QUATERNARY AMMONIUM GERMICIDESAND ALKAMINE OXIDES HAVING REDUCED IRRITATION POTENTIAL,” which wasfiled on Dec. 20, 2006, which application claims priority to U.S.Provisional Patent Application Ser. No. 60/755,569, entitled“ANTIBACTERIAL COMPOSITIONS COMPRISING QUATERNARY AMMONIUM GERMICIDESAND ALKAMINE OXIDES HAVING REDUCED IRRITATION POTENTIAL,” which wasfiled Dec. 30, 2005, both of which are incorporated herein by reference.

FIELD OF INVENTION

The present invention relates generally to antibacterial compositionsexhibiting the antibacterial effectiveness of quaternary ammoniumcompounds and reduced irritation to mammalian tissue.

BACKGROUND

Antibacterial personal care compositions are known in the art.Especially useful are antibacterial cleansing compositions, whichtypically are used to cleanse the skin and to destroy bacteria and othermicroorganisms present on the skin, especially the hands, arms, and faceof the user. Several different classes of antibacterial agents have beenused in antibacterial cleansing compositions. One such agent, quaternaryammonium compounds, are effective cleansing agents, however, thesecompounds can cause irritation to the epithelial tissue of the user,particularly the skin and eye tissue.

Various attempts have been made to mitigate the irritation of quaternaryammonium compounds to the skin and eye. Mitigants have includedcombining quaternary ammonium compounds with nonionic compounds,maltodextrin, urea, benzoate salts, and ethoxylated lanolin oralkoxylated fatty amines. Another mitigant found capable of decreasingirritation has been to combine quaternary ammonium compounds withmixtures of alkamine oxide surfactants with nonionic materials.

While these mitigants provide some comfort to the consumer, a needexists for a phase stable, effective quaternary ammonium germicide thateffectively and sufficiently reduces irritation to animal tissue,particularly skin and eye tissue.

SUMMARY OF THE INVENTION

This summary of the invention is intended to introduce the reader tovarious exemplary aspects of the invention. Particular aspects of theinvention are shown in other sections hereinbelow, and the invention isset forth in the appended claims which alone demarcate its scope.

In accordance with an exemplary embodiment of the present invention, anantibacterial composition that exhibits reduced eye irritancy isprovided. The antibacterial composition comprises a quaternary ammoniumcompound, an alkamine oxide, a nonionic material and water. Thequaternary ammonium compound preferably is present in the amount of fromabout 0.1% to about 5.0% by weight of the composition. The alkamineoxide is preferably present in an amount of from about 0.1% to about 10%by weight of the composition. The nonionic material is preferablypresent in an amount from about 0.3% to about 1.5% by weight of thecomposition.

In an exemplary embodiment of the invention, an antibacterialcomposition is provided wherein the nonionic material is present suchthat the relative weight ratio of the nonionic material to the alkamineoxide, by weight, yields a Permeability Value in the Bovine CornealOpacity and Permeability assay of less than 1.2 while maintainingantibacterial efficacy.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of exemplary embodiments only and is notintended to limit the scope, applicability or configuration of theinvention in any way. Rather, the following description providesconvenient illustrations for implementing various embodiments of theinvention. Various changes to the described embodiments may be made inthe function and arrangement of the elements described without departingfrom the spirit and scope of the invention.

In accordance with an exemplary embodiment of the present invention, theantibacterial composition includes a quaternary ammonium compound, analkamine oxide, a nonionic material, and water and exhibits reducedirritation to animal tissue.

In a preferred embodiment of the invention, the quaternary ammoniumcompound is present in the amount of about from 0.1 to 5.0% by weight ofthe composition. For example, in various exemplary embodiments, thequaternary ammonium compound is benzethonium chloride or benzalkoniumchloride. For example, in a benzethonium chloride embodiment, thebenzethonium chloride is present in the composition in the amount ofabout 1.0% by weight.

In accordance with various embodiments, the amount of alkamine oxidesurfactant present in the composition is related to the amount andidentity of the antibacterial agent in the composition, to the identityof the alkamine oxide surfactant, and the end use of the composition. Ina preferred embodiment of the invention, the alkamine oxide is presentin the amount of from about 0.1 to about 10% by weight. In one exemplaryembodiment, the alkamine oxide is lauramine oxide. In various exemplaryembodiments, depending upon the specific composition, the lauramineoxide is present in varying amounts ranging, preferably, from about 0.3%to about 1.5% by weight.

In accordance with various embodiments, an alkamine oxide useful in thepresent invention contains at least one long hydrocarbon chaincontaining at least eight carbon atoms. One class of amine oxides is thealkyl di(lower alkyl) amine oxides, wherein the alkyl group contains 8to 22, and preferably about 10 to about 16, carbon atoms, and can bestraight or branched chain, saturated or unsaturated. The lower alkylgroups contain 1 to 7 carbon atoms, and typically are methyl. Specificexamples include, but are not limited to, lauryl dimethyl amine oxide,myristyl dimethyl amine oxide, dimethyl cocoamine oxide, dimethyl(hydrogenated tallow)amine oxide, myristyl/palmityl dimethyl amineoxide, myristyl/lauryl dimethyl amine oxide, cetyl dimethyl amine oxide,stearyl dimethyl amine oxide, and myristyl/cetyl dimethyl amine oxide.

Another class of useful amine oxides includes alkyl di(hydroxy loweralkyl)amine oxides in which the alkyl group contains 8 to 22, andpreferably about 10 to about 16 carbon atoms, and can be straight orbranched chain, saturated or unsaturated. Specific examples, include,but are not limited to, bis(2-hydroxyethyl)cocoamine oxide,bis(2-hydroxyethyl)tallow amine oxide, andbis(2-hydroxyethyl)stearylamine oxide.

Additional useful amine oxides are termed alkamidopropyl di(loweralkyl)amine oxides in which the alkyl group contains 8 to 22, andpreferably about 10 to about 16 carbon atoms, and can be straight orbranched chain, saturated or unsaturated. Examples are cocoamidopropyldimethyl amine oxide and tallowamidopropyl dimethyl amine oxide. Furtheruseful amine oxides are termed alkylmorpholine oxides in which the alkylgroup contains 8 to 22, and preferably about 10 to about 16, carbonatoms, and can be straight or branched chain, saturated or unsaturated.Alkamine oxides are commercially available, for example, from StepanCo., Northfield, Ill., and Lonza Inc., Fairlawn, N.J.

The above classes of alkamine oxide surfactants contain a C8-C22 alkylgroup selected from, for example, octyl, decyl, undecyl, lauryl,tridecyl, myristyl, cetyl, stearyl, isostearyl, oleyl, and mixturesthereof. Examples of amine oxide surfactants include, but are notlimited to, decyl dimethylamine oxide, lauryl dimethylamine oxide,stearyl dimethylamine oxide, oleyl dimethylamine oxide, cocodihydroxyethylamine oxide, cetyl N,N-dihydroxyethylamine oxide, oleylN,N-dihydroxyethylamine oxide, cocamine oxide, cocamidopropylamineoxide, lauramidopropylamine oxide, oleamine oxide, oleamidopropylamineoxide, wheat germamidopropylamine oxide, isostearamido-propylamineoxide, stearamine oxide, stearamido-propylamine oxide, cocomorpholineoxide, decylamine oxide, dihydroxyethyl C8-C10 alkoxypropylamine oxide,dihydroxyethyl C9-C11 alkoxypropylamine oxide, dihydroxyethyl C12-C11alkoxypropylamine oxide, dihydroxyethyl cocamine oxide, dihydroxyethylstearamine oxide, dihydroxyethyl tallowamine oxide, hydrogenated tallowamine oxide, hydroxyethyl hydroxypropyl C12-C15 alkoxypropylamine oxide,isostearamidopropyl morpholine oxide, myristamidopropylamine oxide,myristamine oxide, palmitamidopropylamine oxide, palmitamine oxide,PEG-3 lauramine oxide, tallow amidopropylamine oxide, tallow amineoxide, undecylenamidopropylamine oxide, and mixtures thereof. Preferredalkamine oxide surfactants are the alkyl di(lower alkyl)amine oxides inwhich the alkyl group contains about 12 to about 16 carbon atoms,including lauramine oxide, myristamine oxide, cocamine oxide, cetamineoxide, and mixtures thereof.

In accordance with other embodiments of the invention, the compositioncontains a blend of alkamine oxide surfactants. In most preferredembodiments, a first component of the alkamine oxide blend containstwelve or fewer carbon atoms and a second component contains more thantwelve carbon atoms.

In a preferred embodiment of the invention, a nonionic material ispresent in the composition so that the ratio of nonionic material toalkamine oxide by weight yields a composition with a Permeability Value(PERMV) in a Bovine Corneal Opacity and Permeability (BCOP) assay ofless than about 1.2. In an exemplary embodiment, the nonionic materialis a nonionic polymeric surfactant like a copolymer comprised of a blockcopolymer of ethylene oxide and propylene oxide or an alkylpolyglucosidesurfactant. In another exemplary embodiment, the nonionic material isdecyl polyglucose (APG) present in the composition at an amount of about2.5% by weight. In another exemplary embodiment, the nonionic materialis Pluronic F108 present in the composition at an amount of about 2.5%.

In accordance with various embodiments of the invention, the compositionoptionally includes polymeric thickeners of the nonionic or cationicclass, dyes, perfumes, builders, pH adjusters, solvents, and otheradjuvant materials. For example, in an exemplary embodiment of thepresent invention, a polymeric thickener, Natrosol 250HHR CS, isincluded in the composition at an amount of about 1.0% by weight.

In one embodiment of the composition, the pH of the composition isbetween about 5 and 9, preferably between about 6 and 8, and mostpreferably between about 6.5 and 8.

In a still further exemplary embodiment of the invention, theantibacterial composition may be free anionic or zwitterionicsurfactants including sulfates, sulfonates, carboxylates, andaminocarboxylates.

The antibacterial effectiveness of various formulations of thecompositions formed in accordance with the present invention were testedby conducting a Health Care Personnel Hand Wash test, an in vivo test ofefficacy, whereby the survival of challenged organisms exposed toantibacterial test formulation is determined as a function of the numberof hand washes. In general, the Health Care Personnel Hand Wash test iswell known in the antibacterial products industry. In this test, handsof volunteers are inoculated with a volume of bacterial inoculum toconstitute a bacterial challenge to the hands. The volunteers then washtheir hands with the antibacterial composition to be tested, and thiscycle is repeated 11 times. Bacterial reductions are determined afterthe first and eleventh wash.

In this example, two exemplary formulations of antibacterialcompositions were tested using the Health Care Personnel Hand Wash test.Hibiclens, a commercial product, serves as a positive control in thetest. Table 1 summarizes the compositions of the formulations,Formulation 1 and 2.

TABLE 1 Formulation 1 Formulation 2 weight percent Deionized Water 90.2491.54 Natrosol 250HHR CS 1.0 1.0 Benzethonium Chloride 1.0 1.0 PluronicF108 2.5 0.0 Lauramine Oxide 1.5 0.3 Decyl Polyglucose (APG) 0.0 2.5Sodium Phosphate, 10% sol. 0.26 0.46 Total 100.0 100.0 Final pH 7.457.49 Ratio of Nonionic:active 1.7:1 8.3:1 basis of Lauramine Oxide

Table 2 summarizes the antibacterial performance of these formulationsas measured by the Health Care Personnel Hand Wash test:

TABLE 2 Log10 Bacterial Reduction Wash 1 Wash 11 Formula- HibiclensHibiclens tion Formula Placebo (+control) Formula Placebo (+control) 12.49 2.04 2.7 3.02 2.62 3.52 2 2.53 1.77 3.27 3.13 1.90 4.30

The above results illustrate the enhanced antibacterial effectiveness ofantibacterial compositions formed in accordance with various embodimentsof the present invention. Both formulations achieved log reductions ofgreater than 2 on the first wash and greater than 3 on the 11th wash.Additionally, both formulations exhibit superior antibacterialeffectiveness as compared to the placebo. Thus, both formulationsproduce a preferred log reduction and provide sufficient performance.

The reduced potential for eye irritation of various formulations of thecompositions formed in accordance with the present invention wasconducted using a Bovine Corneal Opacity and Permeability (BCOP) assay.The BCOP assay is known in the consumer products industry as an in vitrotest for eye irritation potential. For surfactant-based formulations,the Permeability Value (PERMV) is also a measure of potential irritancyin the BCOP assay. Specifically, the Permeability Value is the OpticalDensity at 490 nm (OD490) determined with a spectrophotometer. It isused to measure the potential for eye irritation with higher irritationpotential corresponding to higher Permeability Values. For personalcleansing compositions like liquid hand soaps, shower gels, and thelike, an appropriate harsh control (control with high known potentialfor eye irritation) has a (PERMV) of 1 or higher. For example, acommercial liquid hand soap that is recognized as having potential forcausing eye irritation has a (PERMV) of 1 to 1.125 in the BCOP assay. Ingeneral, compositions with PERMVs less than 1 are preferred in the art.

In this example, various embodiments of antibacterial compositions weretested using the BCOP assay. Table 3 summarizes the base formulationused while varying the ratio of nonionic material to lauramine oxide andmeasuring the resulting PERMV score.

TABLE 3 Base Formulation weight percent Deionized Water VariableNatrosol 250HHR CS 1.0 Benzethonium Chloride 1.0 Lauramine oxide 0.3% or1.5% Nonionic material (Pluronic F108 or variable decyl polyglucoside)Total 100%

Table 4 summarizes the impact of the ratio of decyl polyglucoside tolauramine oxide (N:A) on PERMV in the BCOP assay.

TABLE 4 Lauramine oxide 1.5%, by weight Lauramine oxide 0.3%, by weightN:A PERMV N:A PERMV 0:1 1.776   0:1 0.854 1.7:1   1.784 6.8:1 0.437 2:11.533 8.3:1 0.66* 3:1 1.971 8.5:1 0.812 *Formulation 2, as above

Table 4 reveals that lauramine oxide is a key determinant of PERMVvalues. Lower lauramine oxide levels leads to lower PERMV, and hencelower eye irritation potential. Additionally, this example illustratesthe surprising discovery that increasing the N:A ratio leads to lowerPERMV, and hence decreasing eye irritation potential, especially forcompositions with lower amounts of lauramine oxide.

Table 5 summarizes the impact of the ratio of Pluronic F108 to lauramineoxide (N:A) on PERMI in the BCOP assay.

TABLE 5 Lauramine oxide 1.5%, by weight Lauramine oxide 0.3%, by weightN:A PERMV N:A PERMV 0:1 1.776   0:1 0.854 1.7:1   1.342 8.3:1 0.6601.7:1   1.124* 8.5:1 0.532 3:1 1.123 5:1 0.643 7:1 0.587 *Formulation 1,as above

Table 5 also demonstrates that lauramine oxide is the main determinantof PERMV values. Surprisingly however, the PERMV scores, and thepotential fore eye irritation, decrease strongly with increasing N:A,even for formulations with high lauramine oxide content. Without beinglimited by any particular theory, amine oxides appear to be the majordeterminants of irritation in formulations with quaternary ammoniumgermicides. Surprisingly, the ratio of nonionic material to amine oxidecan be used to manipulate the irritation potential of formulations whilemaintaining antimicrobial efficacy at constant germicide concentration.

Many modifications and variations of the invention as set forth can bemade without departing from the spirit and scope thereof, and thereforeonly such limitations should be imposed as are indicated by the appendedclaims.

1-20. (canceled)
 21. An antibacterial composition comprising: aquaternary ammonium compound present in the amount of from about 0.1 toabout 5 percent by weight of the antibacterial composition; one or morealkamine oxides present in the amount of from about 0.1 to about 10percent by weight of the antibacterial composition; one or more nonionicmaterials; one or more liquid carriers; and optionally one or moreingredients selected from a group comprising: polymeric thickeners ofthe nonionic or cationic class, dyes, perfumes, builders, pH adjusters,solvents, and mixtures thereof.
 22. The antibacterial composition ofclaim 21, wherein said quaternary ammonium compound is present in theamount of about 1.0 percent by weight of the antibacterial composition.23. The antibacterial composition of claim 22, wherein said quaternaryammonium compound is selected from a group comprising: benzethoniumchloride, benzalkonium chloride, alkyl dimethylbenzyl ammonium chloride,cetyl trimethyl ammonium chloride.
 24. The antibacterial composition ofclaim 21, wherein said one or more alkamine oxides are present in theamount of from about 0.3 to about 1.5 percent by weight of theantibacterial composition.
 25. The antibacterial composition of claim24, wherein said alkamine oxide is lauramine oxide.
 26. Theantibacterial composition of claim 21, wherein said nonionic material iscomprised of a nonionic polymeric surfactant.
 27. The antibacterialcomposition of claim 26, wherein said nonionic polymeric surfactant is ablock copolymer of ethylene oxide and propylene oxide.
 28. Theantibacterial composition of claim 21, wherein said nonionic material iscomprised of an alkylpolyglucoside surfactant.
 29. The antibacterialcomposition of claim 21, wherein said nonionic material is selected froma group comprising decyl polyglucose and Pluronic F108.
 30. Theantibacterial composition of claim 29, wherein said nonionic material ispresent in the composition at an amount of about 2.5 percent by weight.31. The antibacterial composition of claim 21, wherein said liquidcarrier is water.
 32. The antibacterial composition of claim 21, whereinsaid polymeric thickener is Natrosol 250HHR CS present in thecomposition at an amount of about 1.0 percent by weight.
 33. Theantibacterial composition of claim 21 having a pH between about 5 and 9.34. The antibacterial composition of claim 21 having a pH between about6 and
 8. 35. The antibacterial composition of claim 21 having a pHbetween about 6.5 and
 8. 36. The composition of claim 21, wherein therelative weight ratio of the nonionic material to the alkamine oxideyields a composition with a Permeability Value in a BCOP assay of lessthan about 1.2.
 37. The composition of claim 36, wherein said relativeweight ratio of the nonionic material to the alkamine oxide is fromabout 0:1 to about 8.5:1.
 38. The antimicrobial composition of claim 37,wherein said relative weight ratio of the nonionic material to thelauramine oxide is from about 5:1 to about 7:1.
 39. The composition ofclaim 21, wherein said composition is free of anionic and zwitterionicsurfactants.
 40. The composition of claim 39, wherein said surfactantscomprise a sulfate, sulfonate, carboxylate, aminocarboxylate, andmixtures thereof.
 41. The antimicrobial composition of claim 21, whereinsaid composition exhibits a log reduction of at least 2 after the firstwash and a log reduction of at least 3 after the eleventh wash in aHealth Care Personnel Hand Wash test, as measured bacteria.